False elevation of serum CA-125 level caused by human anti-mouse antibodies

Discordant results were observed for serum CA-125 (carbohydrate antigen-125) assays in a patient who was monitored for recurrence of ovarian cancer. Serum CA-125 levels in this patient were normal when measured in one laboratory, but >5-times the upper limit of normal (35 U/mL) when measured in another laboratory. Both laboratories used dual antibody heterogeneous immunoassays, but from different manufacturers. Cross-linking heterophilic antibodies were suspected as a cause of the discrepancy, but the interference was not alleviated after 10-fold dilution. Assay of the patient's serum for human anti-mouse antibodies was positive, but only slightly above the reference range. Addition of blocking antibodies eliminated the interference, showing that human anti-mouse antibodies were the cause of the discrepant CA-125 results. These findings indicate that relatively low concentrations of human anti-mouse antibodies can cause significant interference in two-site immunoassays.